Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all‐trans retinoic acid and arsenic trioxide

Abstract

Summary Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5–10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m2/d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of complete cytogenetic response was 43% (n = 6) and the rate of complete molecular response was 21% (n = 3). Relapse was frequent with 7 of 9 responders relapsing after a median of 4·6 months (range 1·6–26·8 months). The median event-free survival (EFS) was 3·5 months [95% confidence interval (CI) 0–8·6 months] and the median overall survival (OS) was 9·5 months (95% CI 5·9–13·1 months). These results demonstrate that tamibarotene has activity in relapsed APL after treatment with ATO and ATRA and further studies using tamibarotene as initial therapy and in combination with ATO are warranted.

Acute Promyelocytic Leukemia: A History over 60 Years—From the Most Malignant to the most Curable Form of Acute Leukemia

“…Tamibarotene (formerly called Am80), a synthetic retinoic acid with more potent in vitro activity than ATRA, has demonstrated a favorable pharmacokinetic profile, as the plasma level does not decline after daily administration [259]. It produced interesting results when used as a single agent for induction in relapsed/refractory patients who previously received ATRA and ATO [260]. In a study reported by the Japan Adult Leukaemia Study Group, tamibarotene led to an improvement in relapse-free survival (RFS) when used as a maintenance therapy in high-risk APL [110].…”

Management of relapsed and refractory childhood acute promyelocytic leukaemia: recommendations from an international expert panel

“…Tamibarotene, a synthetic retinoid drug, can overcome ATRA resistance and appears promising in relapsed/refractory APL patients (Sanford et al , ). Furthermore, oral ATO is effective in relapsed children where home‐based therapy is desirable (Au et al , ).…”

Current standard treatment of adult acute promyelocytic leukaemia

“…Overall response rate was 64% with 21% mCR. Relapses were frequent after a median of 4·6 months (Sanford et al , ). These data suggest activity efficacy of tamibarotene in advanced disease; its use in association with ATO will probably be explored in the near future.…”